Alcohol's Metabolism Could Be the Key to Its Risks

Heavy drinking increases the risk of a variety of negative health consequences from liver disease to cancer. But some people who drink heavily appear to be at a greater risk for developing these problems than others.

Researchers believe the difference between those with greater risk and those with lower risk may involve how the body metabolizes, or breaks down and eliminates alcohol, which can vary widely from individual to individual.

How Fast Is Alcohol Metabolized?

No matter how much alcohol you consume, your body can only metabolize a certain amount every hour. Alcohol is metabolized at a rate of approximately one drink per hour. When more than this is consumed, it builds up in the body and causes intoxication.

So if you consume a single drink, you may return to a blood alcohol concentration (BAC) of 0.00 in an hour or two. If you consume a larger amount of alcohol in a short period of time, it will take much longer for your liver to metabolize it.

The results illustrate the fact that the body can only break down and eliminate so much alcohol per hour. It is important to remember that these times are averages.

How the Body Metabolizes Alcohol

When alcohol is consumed, it is absorbed into the blood from the stomach and intestines. Then enzymes, bodily chemicals that break down other chemicals, begin to metabolize the alcohol.

Two liver enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), begin to break apart the alcohol molecule so it can eventually be eliminated from the body. ADH helps convert alcohol to acetaldehyde. Acetaldehyde is only in the body for a short time because it is rapidly converted to acetate by other enzymes.

Most of the alcohol is metabolized by the liver as described above, but small amounts are eliminated from the body by forming fatty acid ethyl esters (FAEEs), compounds that have been found to damage the liver and pancreas.

Lastly, a small quantity of alcohol is not metabolized and is instead eliminated in the breath and urine, which is how BAC is measured in breath and urine tests.

The Dangers of Acetaldehyde

Acetaldehyde can cause significant damage to the liver because that is where most alcohol is broken down into the toxic by-product. That said, some alcohol is instead metabolized in the pancreas and the brain, where acetaldehyde can also damage cells and tissues.

Small amounts of alcohol are metabolized in the gastrointestinal tract, which acetaldehyde can also damage. Some researchers believe the effects of acetaldehyde go beyond the damage it can cause to tissues but might also be responsible for some of the behavioral and physiological effects attributed to alcohol.

Animal studies have found that acetaldehyde in the brain contributes to alcohol's behavioral effects. Such effects can include loss of judgment, decreased concentration, and impaired coordination.

Acetaldehyde and Impairment

When researchers administered acetaldehyde to laboratory animals, it caused incoordination, memory impairment, and sleepiness. Conventional thinking suggests that acetaldehyde alone can't cause these effects because the brain protects itself from toxic chemicals in the blood with its unique blood-brain barrier.

Nevertheless, when the enzymes catalase and CYP2E1 metabolize alcohol—which only happens when large amounts are consumed—acetaldehyde can be produced in the brain itself.

Acetate, one of the products of the breakdown of acetaldehyde, can cross the blood-brain barrier where it impacts GABA, an inhibitory transmitter. This inhibitory effect can then lead to impaired motor function.

Genetics and Metabolism

The size of the liver and body mass of the drinker are factors in how much alcohol a person can metabolize in an hour, but research tells us that the genetic makeup of the individual is probably the most significant factor in how efficiently alcohol is broken down and eliminated.

Variations of ADH and ALDH enzymes have been traced to variations in the genes that produce these enzymes. Some people have ADH and ALDH enzymes that work less efficiently than others, while others have enzymes that work more effectively.

Simply put, this means some people have enzymes that can break down alcohol to acetaldehyde or acetaldehyde to acetate, more quickly than others.

The Difference Between Women and Men

Women absorb and metabolize alcohol differently from men. Research has shown that women may have less ADH enzyme activity in the stomach, allowing a larger percentage of alcohol to reach the blood before being metabolized.

This could be one reason women who drink are more susceptible to alcohol liver disease, heart muscle damage, and brain damage than men.

Genetics and Alcoholism

Genetics can also be a factor in whether or not the person is susceptible to developing alcohol use disorders.

For example, there is one variation of these enzymes that causes a build-up of acetaldehyde to the point it causes facial flushing, nausea, and a rapid heart rate. These effects can occur with even moderate alcohol consumption.

Their gene variant has a protective effect against developing alcoholism. That protective gene, ADH1B*2, is rarely found in people of European and African descent. Another variant, ADH1B*3, is found in around 25% of Black people and protects against alcoholism.

That said, some research indicates that variations of the ALDH enzyme, ALDH1A1*2, and ALDH1A1*3 may be associated with alcoholism in Black individuals.

It's Not All Genetic

According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), about half the risk of developing an alcohol use disorder stems from genetics. That means our genes play an important part, but other factors also make up half of the story.

Children of people with alcohol use disorder are more likely than the general population to develop problems with alcohol use. This increased risk may, in part, be a result of some shared genetic factors, but experts also believe that shared environmental and social factors likely are at play as well.

For example, research has found that alcohol use disorders increased in people of Japanese descent from 2.5% to 13% between 1979 and 1992 among those who carried the protective ADH1B*2 gene. This suggests that other factors can overcome protective genetic effects.

Alcohol's Health Consequences

Heavy or chronic alcohol consumption has been linked to a long list of negative health consequences and long-term adverse effects. Some of these health problems have been directly linked to how alcohol is metabolized in the body and the production of acetaldehyde.

Cancer

The toxic effects of acetaldehyde have been linked to the development of cancers of the mouth, throat, upper respiratory tract, liver, colon, and breasts.

Although they are less likely to drink large amounts of alcohol, these people are at greater risk for developing cancer because their bodies produce more acetaldehyde when they do drink. So, even some moderate drinkers are a greater risk of developing cancer.

Alcohol-Related Liver Disease

Because the liver is the organ that metabolizes most of the alcohol in the body, it is where most of the acetaldehyde is produced, it is particularly vulnerable to the effects of alcohol metabolism. More than 90% of heavy drinkers develop fatty liver.

Alcohol-Related Pancreatitis

Because some alcohol metabolism also takes place in the pancreas, it is exposed to high levels of acetaldehyde and FAEEs. However, around 10% to 15% of heavy drinkers develop alcoholic pancreatitis, indicating that alcohol consumption alone is not the only factor in developing the disease.

Increased Body Weight

Alcohol consumption does not necessarily lead to increased body weight, in spite of its relatively high caloric value. Although moderate alcohol consumption does not lead to weight gain in lean men or women, studies have found that alcohol added to the diets of overweight people does lead to weight gain.

Effects on Sex Hormones

In men, alcohol metabolism contributes to testicular injury and impairs testosterone synthesis and sperm production. Prolonged testosterone deficiency may contribute to feminization in males, such as breast enlargement.

In women, alcohol metabolism may cause increased production of estradiol and decreased estradiol metabolism, resulting in increased levels. Estradiol contributes to increased bone density and a reduced risk of coronary artery disease.

Interactions With Medication

Alcohol consumption affects the metabolism of many different medications, increasing the activity of some and diminishing the effectiveness of others.

Metabolism-Based Treatment

National Institute on Alcohol Abuse and Alcoholism-funded research continues to examine how variations in the way the body metabolizes alcohol may influence why some people drink more than others and why some develop serious alcohol-related health problems.

Researchers believe how the body breaks down and eliminates alcohol may hold the key to explaining the differences, and continued research may help in developing metabolism-based treatments for people who drink and are at risk for developing alcohol-related health problems.

Current evidence-based treatments for alcohol use disorder include:

• Psychotherapy: Therapy focuses on helping people identify triggers, set goals, and develop coping skills. Common types of therapy that may be used to treat alcohol use problems include cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), contingency management (CM), and acceptance- and mindfulness-based interventions.
• Medications: Certain medications may be prescribed to reduce cravings and withdrawal. Some medications that may be prescribed include acamprosate, disulfiram, or naltrexone.
• Support groups: Mutual support recovery groups, such as 12-step facilitation, can also be helpful for long-term recovery. Such groups can provide encouragement and may increase the chances that someone remains sober over time.

Treatments vary depending on the needs of the individual. A combination of therapy, medications, and 12-step facilitation can be the most effective in many cases.